The present invention relates to rifaximin (Common International Denomination) which is the compound 4-desoxy-4'-methyl-pyrido [1'2':1.2] imidazo [5.4-c] rifamycin SV, which is described in Italian Patent 1,154,655 and in U.S. Pat. No. 4,341,785. The substance has been described to be endowed with an antibacterial activity similar to the activity of rifampin [Venturini A. P. and Marchi E., Chemiotherapia, 5 (4), 257-256, (1986)]. However, its mechanism of action differs from rifampin in that it is not absorbed through the systemic route after oral administration [Venturini A. P., Chemotherapy, 29, 1-3, (1983) and Cellai L. et al., Chemiotherapia, 3, (6), 373-377, (1984)] due to the zwitterionic nature of the compound, which cannot be absorbed by the gastrointestinal tract [Marchi E. et al., J. Med. Chem., 28, 960-963, (1985)].
Due to this particular pharamcokinetic behavior, rifaximin has no toxicity at a dose of 2000 mg/kg/os, when administered orally in rats, and therefore, on the basis of the microbiological pharmacodynamic and toxicological data, this substance has been used as a drug for the therapy of bacterial gastroenteritis, neurological symptoms and clinical symptoms of hepatic encefalopathy and for the pre- and post-surgical treatment of the gastrointestinal tract [Alvisi V. et al., J. Int. Med. Res., 15, 49-56, (1987), Testa R. et al., Drugs Exptl. Clin. Res., 11, 387-392, (1985), Gruttadauria G. et al., Eur. Rev. Med. Pharm. Sci., 9, 100-105, (1987)].
The present invention relates to a novel therapeutic use of rifaximin in the treatment of vaginal infections, in particular bacterial vaginosis, because this antibiotic has now been shown to exhibit excellent activity in vitro (MIC) with respect to microorganisms such as Bacteroides bivius-disiens, Gardnerella vaginalis, Mobiluncus spp., Neisseria gonorrhoeae, Lactobacillus spp. and Haemophilus ducreyi, in addition, Chlamydia trachomatis, another organism, infecting the vaginal tract, has shown susceptibility to rifaximin.
The main cause of vaginal symptoms in women is due to bacterial vaginosis, which is characterized by an increase in the vaginal secretion of a white grayish color and which has a bad odor. This vaginal fluid shows the presence of bacterial flora which comprises mainly anaerobic bacteria such as Gardnerella vaginalis and the species Bacteroides, Mobiluncus and Lactobacillus, other aerobic bacteria such as Haemophilus ducreyi and Neisseria gonorrhoeae may also cause vaginal symptoms. Further the chemical composition shows an alteration in the presence of organic acids with increase of succinates and decrease of lactates in addition to the presence of some amines which have bad odor such as putrescine, cadaverine and trimethylamine.
Bacterial vaginosis generally shows scanty or no inflammation of the vaginal epithelium and resembles more of an alteration of the bacterial vaginal ecosystem than a real and proper infection of tissues or epithelium. This pathology is currently being treated mainly with metronidazole, clindamycin or ampicillin administered orally, but this method of use by the systemic route is frequently accompanied by serious side effects. In fact, metronidazole exhibits serious side effects particularly on the blood and on the central nervous system so much that in certain types of patients it has been necessary to discontinue the treatment and authorities in the medical field have recommended that women who use metronidazole should not breast feed (Martindale--The Extra Pharmacopoeia--29th Edition--1989--page 667).
Clindamycin also exhibits serious side effects, particularly on the gastrointestinal tract with serious forms of diarrhea and pseudo-membranous colitis that can even lead to the death of the patient (Martindale--The Extra Pharmacopoeia--29th Edition--1989--pages 198-199).
Rifaximin is not absorbed by the oral route [Venturini A. P., Chemotherapy, 29, 1-3, (1983)] nor by topical application [Venturini A. P. et al., Drugs Exptl. Clin. Res., 13, 4, 233-6, (1987)]. Compared with drugs currently used, rifaximin unquestionably exhibits a very substantial advantage, since there are no side effects.